Swelling in the legs after taking hypertension medication... What are the side effects of blood pressure lowering drugs?

Antihypertensive drugs are broadly divided into five categories: ▲Diuretics ▲Sympathetic nerve blockers ▲Calcium channel blockers ▲Angiotensin-converting enzyme inhibitors ▲Angiotensin receptor blockers. According to Dr. Kim Ye-ji, Academic Director (Pharmacist) of the Korean Pharmaceutical Association, diuretics inhibit the reabsorption of water and sodium in the distal tubules, lowering blood pressure; sympathetic nerve blockers reduce the force of heart contractions, decreasing the amount of blood pumped from the heart at once, thereby lowering blood pressure. Calcium channel blockers block calcium channels in vascular smooth muscle, causing vasodilation and lowering blood pressure. Angiotensin-converting enzyme inhibitors suppress the enzyme that produces angiotensin II, which constricts blood vessels, while angiotensin receptor blockers prevent angiotensin II from binding to its receptors, thereby dilating blood vessels and lowering blood pressure.

There are various products, but if we were to pick one from each category: for diuretics, Korea Pfizer's 'Aldactone Tablet'; for sympatholytic agents, Hyundai Pharm's 'Tenomin Tablet'; for calcium channel blockers, HKE Innoen's 'Herben Tablet'; for angiotensin-converting enzyme inhibitors, Boryung's 'Capril Tablet'; and for angiotensin receptor blockers, DKSH Korea's 'Atakan Tablet'. In the case of hypertension patient Ms. Lee, HanDok's 'Lasix Tablet' is a diuretic, and TwinStar Tablet is a combination drug containing calcium channel blocker and angiotensin receptor blocker components. Atakan Plus Tablet is also a combination drug, containing both angiotensin receptor blocker and diuretic components.

Academic Director Kim Ye-ji and Professor Won Ho-yeon of the Cardiology Department at Chung-Ang University Hospital identified angiotensin receptor blockers as the most commonly prescribed antihypertensive drugs. According to IQVIA, a pharmaceutical market research firm, the angiotensin receptor blocker 'Atacand' alone recorded sales of approximately 35 billion won in Korea in 2022. Professor Won Ho-yeon stated, "Angiotensin receptor blockers have a similar mechanism to angiotensin-converting enzyme inhibitors, but they directly inhibit angiotensin II, which reduces the occurrence of side effects."

According to Professor Won, combination therapy with an angiotensin receptor blocker and a calcium channel blocker is preferred in two-drug combination prescriptions. The previously mentioned TwinStar tablets are a combination of an angiotensin receptor blocker and a calcium channel blocker. Yuhan Corporation, the sales partner of Korea Boehringer Ingelheim for TwinStar tablets, recorded sales of 81.6 billion won last year.

Side effects vary slightly depending on the type of medication. ▲Diuretics may cause hypotension, dizziness, and hypokalemia ▲Sympathetic nerve blockers may cause bronchoconstriction and peripheral vasoconstriction ▲Calcium channel blockers may cause peripheral edema, constipation, and bradycardia ▲Angiotensin-converting enzyme inhibitors may cause hyperkalemia, dry cough, and angioedema ▲Angiotensin receptor blockers may cause hyperkalemia and other side effects.

In the case of Auntie Lee (84), who has hypertension, she was taking 'TwinStar Tablets' from Korea Bayer Schering Ingelheim to lower her blood pressure. One day, her legs swelled abnormally, and when she went to the hospital, the doctor told her it was a side effect of her usual antihypertensive medication. After switching her medication to DKSH Korea's 'Atakan Plus Tablets' and Han Dok's 'Laxis Tablets,' and reducing the dosage, the swelling improved.

This is because the 'TwinStar Tablets' that caused swelling in hypertensive patient Mr. Lee contained a calcium channel blocker ingredient. 'Atacan Plus Tablets' and 'Lasix Tablets' contain diuretic ingredients, which have a lower probability of causing swelling.

If you experience side effects from your existing hypertension medication like Lee, you should consult your primary care physician. Professor Won Ho-yeon said, "When a common side effect of angiotensin-converting enzyme inhibitors, such as cough, occurs, it is usually changed to an angiotensin receptor blocker," and "There isn't a strict protocol for which medication to switch to when side effects appear; prescriptions vary depending on the patient's condition." Understanding the type and severity of side effects can help determine whether to continue taking the medication causing the side effects while only reducing the dosage. There are also cases where it is unavoidable to stop the current medication and switch to a different one.

Academic Director Kim Ye-ji said, "Side effects vary greatly depending on the patient, and the same medication can cause issues in some patients but not in others," and added, "It is important to consult with a doctor to find the most appropriate medication for the patient."

It is important to take hypertension medication regularly at the same time every day. What should you do if you forget to take your medication? You should not take double the dose by combining the missed dose with the next scheduled dose. Dr. Yeji Kim, Medical Director, said, "If you forget whether you've taken your medication and end up taking it twice, it can cause low blood pressure, dizziness, and increase the risk of falls," and emphasized, "You should never take two pills at once." Once you realize you've missed a dose, it is better to take only the amount you were originally supposed to take.

A drug is currently under development that can control blood pressure with a single injection, lasting for 3 to 6 months, to solve this inconvenience. Last July, the pharmaceutical company Roche partnered with Alnylam to develop an RNA interference therapy called Zilebesiran. It works by blocking the gene responsible for producing angiotensinogen, a precursor to angiotensin II that constricts blood vessels, thereby lowering blood pressure for up to six months. Professor Won Ho-yeon and Academic Director Kim Ye-ji identified Zilebesiran as a promising new hypertension drug to watch.

Gilevesiran met the primary endpoint in a Phase 2 clinical trial (KARDIA-1) conducted last September on adult patients with mild to moderate hypertension. Hypertensive patients treated solely with Gilevesiran showed an average reduction of 14.5 mmHg in systolic blood pressure after six months compared to those given a placebo. In April of this year, results from a Phase 2 study (KARDIA-2) were announced, involving patients whose blood pressure remained uncontrolled despite existing antihypertensive treatment. In this study, 672 patients with uncontrolled hypertension were administered either 600 mg of Gilevesiran or a placebo and followed up. The Gilevesiran group experienced a statistically significant reduction in 24-hour ambulatory systolic blood pressure by an average of 4 to 12 mmHg compared to the placebo group.